The object of this project is to carry out the synthesis and evaluate some of the biological and behavioral properties of analogs of the methionine-enkephalin pentapeptide. In this way, it should be possible to elucidate conformational properties and mechanisms of action of the opiates and to develop analogs with increased analgesic activity particularly after peripheral administration. The design of long-sought, non-tolerance producing, non-addictive analgesics would require the synthesis of peptides with prolonged biological half-lives and an ability to cross the blood-brain barrier after systemic application. Analog studies will continue on the C61-91 fragment of beta-lipotropin, beta-endorphin, which have been made possible by the development of rapid and efficient synthetic methods for this large 31 residue molecule. We would hope to derive far more potent forms of this peptide which should be more practical from a potential therapeutic viewpoint given the high cost of making these long peptides. Basic studies on the effects of the opiate peptides on gastrointestinal and other peripheral processes will continue.